Primary mitochondrial myopathy is a rare genetic disorder that occurs when there are mutated
mitochondria in muscle cells, especially skeletal muscle cells. These mitochondria are unable
to generate adenosine triphosphate, or ATP, which is a form of energy used by our cells.
As a result, muscle cells, which require a lot of energy to function, stop functioning
properly.
The mitochondria are the main energy producing factories of a cell, and they do so with the
help of the electron transport chain, and the enzyme ATP synthase. The electron transport
chain is made up of complexes of proteins or lipids, called electron carriers, embedded
within the inner mitochondrial membrane which pass electrons along like the baton in a relay
race. This movement of electrons helps establish a proton gradient that drives ATP synthase
to phosphorylate adenosine diphosphate or ADP into ATP.
Primary mitochondrial myopathy is caused by a mutation either in the mitochondrial DNA
or nuclear DNA, which results in the abnormal production of mitochondrial proteins, impairing
the function of the electron transport chain. Mutations in the nuclear DNA are commonly
inherited in an autosomal dominant fashion, which means one mutated gene is enough to
cause the disease; or autosomal recessive fashion, which means two mutated genes, one
from each parent, are needed to cause the disease. Mutations in the mitochondrial DNA
follow maternal inheritance , meaning that only an affected woman can pass on the disease
to her children. This is because, typically during fertilization, the father’s mitochondria
are left behind while the sperm’s nucleus alone enters the egg. The exception is the
mitochondrial DNA single deletion, a common cause of primary mitochondrial myopathy, which
is always sporadic and cannot be transmitted to the offspring.
In primary mitochondrial myopathy, muscle cells are unable to generate ATP, which results
in muscle weakness and fatigue. Sometimes there may also be muscle pain, cramping, stiffness,
or even paralysis of the muscle. Individuals typically develop exercise intolerance, which
is a reduced ability to perform physical activity.
Symptoms vary based on the group of muscles affected. In most individuals, the first to
be affected are the extraocular muscles which control eye movements, which results in progressive
external ophthalmoplegia. Symptoms of progressive external ophthalmoplegia include restricted
eye movements; diplopia, or double vision; and ptosis, or drooping of eyelids. Facial
muscle involvement can cause slurred speech and swallowing difficulty. Involvement of
chest wall muscles results in respiratory failure. Involvement of muscles in the hands
and legs can affect day to day activities like walking, eating and writing.
Diagnosis begins with a physical and neurological examination to rule out central nervous system
involvement. A muscle biopsy is the gold standard test. It shows the characteristic ragged-red
fibers, which are caused by compensatory proliferation of abnormal mitochondria. In addition, biochemical
tests can be done to look for elevated blood lactate levels, high blood lactate to pyruvate
ratio and elevated serum creatinine kinase; and genetic testing can be done to look for
mutations in mitochondrial or nuclear DNA.
While there's no cure for primary mitochondrial myopathy, there are treatment options. Supportive
care can be given to help manage symptoms. In addition, individuals may require regular
exercise to improve muscle function. Supplements called mitochondrial cocktails or “mito-cocktails”
containing vitamins; creatine; antioxidants; and coenzyme Q10, which is a component of
the electron transport chain, can be given to improve mitochondrial activity.
All right, as a quick recap… primary mitochondrial myopathy is a genetic disorder caused by mutations
in the mitochondrial or nuclear DNA, which results in the inability of muscle cells to
produce enough ATP. Common symptoms include restricted eye movements, diplopia, ptosis,
slurred speech, swallowing difficulty, muscle weakness and wasting, and respiratory failure.
Diagnosis is made with the help of a muscle biopsy, biochemical tests for blood lactate
levels, lactate to pyruvate ratio, and creatinine levels; and genetic tests to detect mutations
in the DNA. While there’s currently no cure, treatment includes symptomatic management,
regular exercise, and mitochondrial cocktail supplements.